Lipid Metabolism By Dr. Mohammad
1.
Fatty acid synthesis is low when glucose is low.
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In fasting state and high-diet fat stimulate secretion of anti-insulin hormones which increases the rate of lipolysis in adipose tissues and increases the release and oxidation of free fatty acid.
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Thus ,acetyl-coA carboxylase and fatty acid synthase which are responsible for fatty acid synthesis are inhibited when glucose is low.
2.Severe uncontrolled D.M. is complicated by ketosis, hypercholesterolemia, and fatty liver.
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Severe uncontrolled D.M is complicated by Increased oxidation of FFA increases ketogenesis in liver may lead to ketogenesis, hypercholestremia result from increased synthesis of TAG in liver and decreased clearance of plasma lipoproteins,fatty liver due to over mobilization of depot fat.
3.Excess ethanol intake (alcoholism ) cause hypoglycemia and fatty liver.
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As ethanol intake leads to increase NADH/NAD + ratio , it will lead to inhibiton gluconeogenesis due to reduction of oxaloacetate to malate(in cytosol),thus results in hypoglycemia.
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Inhibition of fatty acid oxidation and increases fatty acid synthesis and esterification for triacylglycerol synthesis resulting in fatty liver.
4.During fasting cholesterol synthesis is low.
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HMG-CoA reductase is the key enzyme for cholesterol synthesis. It is present in two forms active (dephosphorylated) and inactive (phosphorylated).
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The activity of the enzyme is regulated by cAMP dependent enzyme system, increased by carbohydrate feeding and by insulin and decreased by fasting and glucagon.
5. Ethanol intake aggravates gouty status.
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Ethanol intake will lead to increase NADH/NAD ratio .
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This will cause the conversion of pyruvate to lactate ,results in hyperlacticacidemia which in turn decrease the capacity of the kidney to excrete uric acid.
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This leads to increase uric acid in blood (hyperuricemia).That’s why by drinking alcohol, it will aggravates gout.
6. Fate of HMG-CoA in liver mitochondria differs from that in the cytosol
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Fate of HMG- CoA :
 In liver mitochondria : as a substrate in ketone bodies metabolism.
 HMG-CoA undergoes oxidation reaction in liver mitochondria to form acetone and
3-hydroxybutyrate.
 The enzymes used are HMG-CoA synthase and HMG-CoA lyase.
 In cytosol : as a substrate in cholesterol metabolism. HMG-CoA is found in cholesterol synthesis. The enzyme used is HMG-CoA synthase Lipid metabolism

7.Over feeding of carbohydrate causes fatty liver.
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Stimulates lipogenesis, as increase glucose in blood, increase pyruvate, increase active acetate, therefore the availability of substrate for lipogenesis increase thus stimulate lipogenesis
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Carbohydrates feeding stimulates release of insulin,insulin decreases lipolysis
 total effect of increase lipogenesis and decrease lipolysis may lead to fatty liver
8.Hyperthyroidism cause hypocholesterolemia.
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Thyroxine stimulates conversion of cholesterol to bile acid.
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Therefore, increase thyroxine will lead to decrease of cholesterol in blood
(hypocholesterolemia).
9.Aspirin is used to prevent platelet aggregation.
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Aspirin is non stroidal anti-inflammatory drug that inhibit cyclooxygenase pathway by acetylation.
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It will inhibit prostaglandin synthase which catalyze synthesis of prostaglandin, prostacyclin, and thromboxane.
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Thromboxane is responsible for platelet aggregation.
10.Obstructive jaundice cause hypercholesterolemia.
.
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About 1gm of cholesterol is excreted daily, 50% in the form of bile acid and 50% in the form of cholesterol.
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Bile acid are excreted in bile through bile duct. However, in obstructive jaundice, there is blockage of common bile duct (stone or tumor).
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Hence, there is a decrease in excretion of cholestrol and bile acids.
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This lead to accumulation of cholesterol and bile acid in liver. The liver provide plasma cholesterol.
11.HDL promotes the prevention of coronary artery risk disease.
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HDL are endocytosed by the liver cells , where CE are hydrolyzed . The free cholesterol released either:
 Repacked in to lipoprotein
 Converted to bile acid OR
 Secreted in bile.
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This will decrease the cholesterol level in blood, reducing the risk of deposition of cholesterol in arterial wall, as it removes cholesterol from tissue to liver. (reverse cholesterol transport)
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Thus, high level of HDL protect against atherosclerosis, which prevent the coronary artery risk disease. *atherosclerosis is depositon of lipid especially cholesterol and cholesterol ester in arterial wall.

12. LONG CHAIN ACYL-COA INHIBITS FATTY ACID SYNTHESIS.
Free fatty acid will be converted to the acyl-CoA by the reaction of Acyl-CoA synthetase. The long chain acyl-CoA produces metabolic feedback inhibition of the acetyl-CoA carboxylase which is the key enzyme for the fatty acids synthesis.
13. STATINS (LIKE LOVASTATIN) AND THYROID HORMONES (AS IN HYPERTHYROIDISM)
REDUCE PLASMA CHOLESTEROL LEVEL.
Thyroxine stimulates conversion of cholesterol to bile acids. In hyperthyroidism, more cholesterol is converted to bile acids, therefore plasma cholesterol level is reduces.
14. METHYL DONORS ARE LIPOTROPIC FACTORS.
Lipotropic factors are substances needed for synthesis of plasma lipoproteins. One of these factors is choline and methyl donors or compounds. Methyl donors such as glycine betaine, folic acid and vitamin B
12
needed for the synthesis of methyl group, which required for methylation of ethanolamine to form choline.
Dr. Mohammad A. R. Ismaiel
College of science for Women /Babylon University